Humberto Monge

NEUROLOGICAL COMPLICATIONS OF LIVER TRANSPLANTATION IN ADULT VERSUS PEDIATRIC PATIENTS

Neurological complications are important contributors to morbidity and mortality after liver transplantation. We reviewed 391 patients who underwent 427 consecutive orthotopic liver transplantations to analyze the clinical features of patients who experienced one or more neurological complication (74 patients [19%]) and to compare postoperative neurological problems in adults versus children. Neurological complications were more frequent in adults (64 of 273 patients [23%]) than children (10 of 118 patients [8%]) (P < 0.01). The most common neurological complication was encephalopathy (59%), which ranged widely in severity and occurred with similar frequency in adults and children. Other common neurological complications were seizures (12 patients), brachial plexus and peripheral nerve injuries (16 patients, 15 of whom were adults), stroke (5 patients), and central nervous system infections (5 patients). In 27 patients, drug toxicity was the primary cause of neurological complications, all of which reversed with dosage reduction or discontinuation of drug. Cyclosporine and FK506, primarily during intravenous administration for induction of immunosuppression, accounted for 25 of 27 drug-induced neurological complications, which included encephalopathy, seizures, severe tremor, and severe headache. Despite a higher rate of neurological complications in adults, those in children were more severe and associated with a higher mortality rate. When compared with liver transplant recipients without neurological complications, patients with neurological complications had a higher posttransplant mortality rate (14% vs. 5% for adults, and 50% vs. 7% for children). In conclusion, neurological complications after liver transplantation are more common in adults, more severe and associated with a higher mortality rate in children, and associated with a higher mortality rate in both children and adults when compared with transplant recipients without neurological complications.

Long-term outcomes in pediatric liver recipients: Comparison between cyclosporin A and tacrolimus

Cao S, Cox KL, Berquist W, Hayashi M, Concepcion W, Hammes GB, Ojogho OK, So SKS, Frerker M, Castillo RO, Monge H, Esquivel CO. Long‐term outcomes in pediatric liver recipients: Comparison between cyclosporin A and tacrolimus. Pediatr Transplantation 1999: 3: 22–26.

Posttransplant lymphoproliferative disorders and gastrointestinal manifestations of Epstein-Barr virus infection in children following liver transplantation

BACKGROUND Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). METHODS This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). RESULTS After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. DISCUSSION In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.

Resection versus transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma is responsible for more than 1 million deaths per year worldwide and thus remains a challenging medical problem. It causes few or no symptoms and the tumour frequently reaches an enormous size by the time of diagnosis in countries where screening is seldom used. It is generally resistant to commercially available anti‐neoplastic agents and radiation therapy. The principal treatment continues to be resection, either partial or complete, with liver transplantation. However, less than one‐third of patients are surgical candidates for either resection or transplantation at the time of clinical presentation. This review will address the results observed following resection or transplantation for hepatocellular carcinoma.

Potential Effect of Cyclosporin A in Formation of Cholesterol Gallstones in Pediatric Liver Transplant Recipients

Recent advancements in liver transplantationhave resulted in extended survival both for grafts andrecipients. Such improvement, together with the shortageof donor organs has prompted expansion of the donor pool to include less than ideal donors,especially in life-threatening situations. The use ofolder liver donors has been associated with lowerlong-term survival. However, potential morbidity such as gallstone formation has not been explored.We analyzed bile composition in a child who developedcholesterol gallstones in the proximal bile duct twoyears after undergoing emergency liver transplantation with a liver from a 78-year-old donor. Oraladministration of ursodeoxycholic acid (ursodiol)shifted the cholesterol composition of the bile from asupersaturated, potentially crystallized state to aliquid (micellar) state. Unlike cyclosporin A, FK506showed an increase in the proportion of chenodeoxycholicacid and a decrease in the proportion of cholic acid,and thus may exhibit minimal or no hepatotoxic effect. Thus, in donor livers with factorsknown to be associated with cholesterol gallstoneformation (such as age, sex, or obesity), one mayconsider analyzing the bile composition at the time ofprocurement. Depending on cholesterol and bile acidcomposition, the use of FK506 with or without additionof ursodeoxycholic acid may be warranted.

Emergency transjugular intrahepatic portosystemic shunt (TIPS) in an infant: A case report

Since the first successful report regarding the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) as an alternative to surgical decompression of portal hypertension, this method has been used extensively as a temporizing measure in controlling refractory variceal bleeding before liver transplantation in adults with cirrhosis. There are few reports of TIPS in pediatric patients because variceal bleeding in most of these patients can often be managed conservatively without invasive intervention. Recently, successful use of TIPS to treat complications of portal hypertension has been described in two children ages 10 and 13. To our knowledge, there are no reports of TIPS used in infants under the age of 1 year. The authors report a case in which TIPS was used to successfully control variceal bleeding in a 10-month-old infant before consideration for hepatic transplantation.

Does Asian race affect hepatitis B virus recurrence or survival following liver transplantation for hepatitis B cirrhosis

To assess whether Asian race is an independent variable affecting survival and hepatitis B virus (HBV) recurrence after liver transplantation, the results of 27 consecutive liver transplants performed between June 1994 and April 1997 for HBV cirrhosis were analysed. In the group of 13 Asians, 38% had associated hepatocellular carcinoma and 62% had positive hepatitis B virus early antigen (HBeAg) or elevated HBV‐DNA before transplant. Prophylactic hepatitis B immunoglobulin (HBIG) was administered perioperatively and long term at 4–6 weekly interval. Four patients with elevated HBV‐DNA received lamivudine before transplantation. The 3 year actuarial patient survival rate was 100% in both Asian and non‐Asian patients. Twenty‐six patients remained seronegative for hepatitis B virus surface antigen after transplantation. The incidence of post‐transplant HBV recurrence was similar: 0% in Asians compared with 7% in non‐Asians. There was no recurrence in the group of 12 patients who were HBV‐DNA or HBeAg negative pretransplant.

Major hepatic resection without blood transfusion: Experience with total vascular exclusion

Thirty consecutive, major liver resections performed with total vascular exclusion in both non‐cirrhotic and cirrhotic patients were analysed retrospectively. The patients’ ages ranged from 6 months to 80 years. Ten were Asians and five had cirrhosis associated with chronic hepatitis B or C. There was no perioperative death and the mean hospital stay was 6 days for adults and 9.2 days for children. The average vascular exclusion or warm ischaemia time was 25 min (range 10–55 min) and the average intraoperative blood volume given was 275 mL (range 0–3000 mL) packed red blood cells. Sixty per cent required no intraoperative blood transfusion. The mean total bilirubin and aspartate aminotransferase were 1.0 mg/dL (range 0.3–2.3 mg/dL) and 84 IU/L (range 14–306 IU/L) when measured prior to discharge at postoperative day 4–7. In our experience, total vascular exclusion is invaluable in major or difficult liver resections, especially lesions adjacent to the hepatic veins and vena cava. It is associated with a low blood transfusion requirement and a low incidence of complications. It further obviates the need for dissection of the porta hepatis and its associated risks. Total vascular exclusion time of 30 min appears to be well tolerated, even in patients with compensated cirrhosis.

Liver transplantation for fulminant hepatitis at Stanford University

Background. To review the clinical characteristics and outcomes of 26 patients evaluated for liver transplantation for fulminant hepatic failure at Stanford University and Lucile Packard Children’s Hospital in an attempt to identify risk factors and prognostic predictors of survival.Methods. A retrospective review of the records of 26 consecutive patients who were evaluated for possible liver transplantation for acute liver failure from May 1, 1995, to January 1, 2000. Pretransplant patient demographics and clinical characteristics were collected, and the data were analyzed by univariate and multivariate analysis.Results. Clinical assessment of encephalopathy did not predict outcome. Patients with abnormal computed tomography (CT) of the brain had a twofold increase in mortality compared with those patients with normal studies (p = 0.03). Patients requiring mechanical ventilation and continuous venovenous hemofiltration (CVVH) also had a poor prognosis.Conclusion. Predictors of poor outcome after fulminant hepatic failure include abnormal CT scan, mechanical ventilation, and requirement for hemofiltration.

Spontaneous liver rupture associated with hydatidiform mole pregnancy.

BACKGROUND: Spontaneous liver rupture is a rare occurrence during pregnancy. CASE: A young woman presented early in her pregnancy with severe abdominal pain, tachycardia, and hypotension. She was taken emergently to the operating room with a presumed diagnosis of ruptured ectopic pregnancy. Exploration revealed that her hemoperitoneum resulted from large fractures within her liver. During her resuscitation and treatment, a transvaginal ultrasound scan revealed a hydatidiform molar pregnancy. On resolution of postoperative complications and complete recovery, the patient was discharged home. CONCLUSION: This case illustrates that, although very unusual, hydatidiform molar pregnancies should be considered as a precipitating factor for spontaneous liver rupture.